A Phase I/II Study of Pazopanib (GW786034) and Cyclophosphamide in Patients With Platinum-resistant Recurrent, Pre-treated Ovarian Cancer

This study is currently recruiting participants.
Verified November 2011 by University Hospital Heidelberg
Sponsor:
Information provided by:
University Hospital Heidelberg
ClinicalTrials.gov Identifier:
NCT01238770
First received: November 10, 2010
Last updated: NA
Last verified: November 2011
History: No changes posted

November 10, 2010
November 10, 2010
November 2010
June 2012   (final data collection date for primary outcome measure)
  • Determination of the optimal doses for pazopanib (phase I) [ Time Frame: Phase I during treatment ] [ Designated as safety issue: Yes ]
  • Overall response rate according to RECIST criteria / clinical benefit (stable disease or partial response or complete response) (phase II) [ Time Frame: 12 weeks after start of treatment ] [ Designated as safety issue: No ]
Same as current
No Changes Posted
  • Time to progression (TTP) according to RECIST criteria [ Time Frame: Treatment and FU period ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Treatment and FU period ] [ Designated as safety issue: Yes ]
  • Evaluation of CA125 tumour response [ Time Frame: Treatment and FU period ] [ Designated as safety issue: No ]
  • Safety and tolerability [ Time Frame: Treatment and FU period ] [ Designated as safety issue: Yes ]
  • Assessment of quality of life over time as defined by EORTC-QLQ C 30 and Ovar 28 questionnaire [ Time Frame: Treatment and FU period ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
A Phase I/II Study of Pazopanib (GW786034) and Cyclophosphamide in Patients With Platinum-resistant Recurrent, Pre-treated Ovarian Cancer
A Phase I/II Study of Pazopanib (GW786034) and Cyclophosphamide in Patients With Platinum-resistant Recurrent, Pre-treated Ovarian Cancer

The current trial shall clarify the potential of the multitarget antiangiogenic tyrosinkinase inhibitor GW 786034 (pazopanib) in combination with oral cyclophosphamide as salvage treatment in patients with recurrent, pretreated ovarian cancer.

This study is a prospective open-label, non-randomized multicenter phase I/II trial in order to determine overall response rate of patients with platinum-resistant or refractory recurrent, pretreated epithelial ovarian cancer.

In order to assure adequate toxicity assessment, a phase-I-trial is proponed. Phase II will be performed with MTD.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Epithelial Ovarian Cancer, Which is Platinum Resistant or Refractory, Cancer of the Fallopian Tube or Peritoneal Cancer
Drug: Pazopanib and Cyclophosphamid

Phase I Cyclophosphamid Pazopanib Dose level I 50 mg/day 400 mg/day Dose level II 50 mg/day 600 mg/day Dose level III 50 mg/day 800 mg/day

Cyclophosphamide 50 mg daily orally Pazopanib 400, 600 or 800 mg daily orally

Phase II:

Cyclophosphamide 50 mg daily orally Pazopanib 400, 600 or 800 mg daily orally The dose for the phase II part of the trial will be based on the MTD of phase I.

Other Names:
  • Vortrient
  • Endoxan
Not Provided
Eichbaum M, Mayer C, Eickhoff R, Bischofs E, Gebauer G, Fehm T, Lenz F, Fricke HC, Solomayer E, Fersis N, Schmidt M, Wallwiener M, Schneeweiss A, Sohn C. The PACOVAR-trial: a phase I/II study of pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant recurrent, pre-treated ovarian cancer. BMC Cancer. 2011 Oct 20;11:453. doi: 10.1186/1471-2407-11-453.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
57
March 2015
June 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Subjects must provide written informed consent prior to performance of study specific procedures or assessments, and must be willing to comply with treatment and follow up assessments and procedures.
  2. Female subjects ≥18 years of age
  3. Histologically or cytologically confirmed diagnosis of: epithelial ovarian cancer which is platinum resistant (relapse-free interval < 6 months of a platinum-containing primary or secondary platinum therapy) or platinum refractory (progressive disease during primary or secondary platinum therapy), cancer of the fallopian tube, peritoneal cancer Definition of relapse: Demonstration of measurable or non-measurable tumour according to RECIST criteria by an imaging procedure (where applicable before relapse surgery) or increase in the tumour marker CA-125 to twice the upper laboratory value of normal for the hospital
  4. Patients must have failed available standard chemotherapy regimen (except if medically contraindicated or refused by the patient)
  5. Prior treatment with at least 2 chemotherapy regimens in advanced tumor setting
  6. Performance status ECOG 0 2
  7. Adequate contraception
  8. Adequate organ function
  9. Measurable disease according to RECIST criteria.
  10. Able to swallow and retain oral medication.
  11. A life expectancy of at least 12 weeks.

Exclusion Criteria:

  1. Diagnosis of any second malignancy within the last 5 years, with the exception of basal cell or squamous cell skin cancer or in situ carcinoma of the cervix uteri
  2. History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug. Screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases.
  3. Clinically significant gastrointestinal abnormalities which might interfere with oral dosing

    • Active peptic ulcer disease
    • Known intraluminal metastatic lesion/s with suspected bleeding
    • Inflammatory bowel disease
    • Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation
    • History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment
    • Malabsorption syndrome
    • Major resection of the stomach or small bowel
  4. Any unstable or serious concurrent condition (e.g., active infection requiring systemic therapy).
  5. Prolongation of corrected QT interval (QTc) >480 msecs.
  6. History of any one or more of the following cardiovascular conditions within the past 6 months:

    • Cardiac angioplasty or stenting
    • Myocardial infarction
    • Unstable angina
    • Symptomatic peripheral vascular disease
    • Coronary artery by-pass graft surgery
    • Class II, III or IV congestive heart failure as defined by the New York Heart Association (NYHA)
    • History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulant agents (excluding therapeutic warfarin) for at least 6 weeks are eligible
  7. Macroscopic hematuria
  8. Hemoptysis that is clinically relevant within 4 weeks of first dose of study drug
  9. Evidence of active bleeding or bleeding diathesis
  10. Known endobronchial lesions or involvement of large pulmonary vessels by tumor
  11. Prior major surgery or trauma within 14 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.
  12. Chemotherapy or radiation therapy within 2 weeks prior to the first dose of study drug.
  13. Biological therapy, hormonal therapy or treatment with an investigational agent within 28 days or 5 half-lives, whichever is longer prior to the first dose of study drug.
  14. Prior antiangiogenic therapy.
  15. Is unable or unwilling to discontinue predefined prohibited medications listed in the protocol for 14 days or five half-lives of a drug (whichever is longer) prior to Visit 1 and for the duration of the study
  16. Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or that is progressing in severity.
  17. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib
  18. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
  19. Pregnancy (for women of childbearing potential absence to be confirmed by ß-hCG test) or lactation period or missing contraception of women of childbearing potential (Pearl-Index < 1, e.g. hormonal contraception including the combined oral contraceptive pill, the transdermal patch, and the contraceptive vaginal ring, intrauterine devices or sterilization) during treatment and for at least 6 months thereafter.
  20. More than 3 different chemotherapy regimens in advanced tumor setting
  21. Uncontrolled hypertension
  22. History of ischemic event (stroke, myocardial infarction, unstable angina, TIA, symptomatic peripheral vascular disease)
  23. History or clinical evidence of thrombo-embolic event
  24. History of haemoptysis, cerebral, or clinically significant gastrointestinal haemorrhage in the past 6 months
  25. Active bleeding
  26. Signs/Suspicion of intestinal obstruction
Female
18 Years and older
No
Contact: Michael Eichbaum, PD Dr. med. +49 (0) 6221 5637345 Michael.Eichbaum@med.uni-heidelberg.de
Germany
 
NCT01238770
3107000
Yes
PD Dr. med. Michael Eichbaum, University Hospital Heidelberg
University Hospital Heidelberg
Not Provided
Principal Investigator: Michael Eichbaum, PD Dr. med. Medizinische Fakultät Heidelberg Abteilung für Frauenheilkunde und Geburtshilfe
University Hospital Heidelberg
November 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP